Thrombotic thrombocytopenic purpura: recognition and management

Abstract

Thrombotic thrombocytopenic purpura is a life-threatening multisystem disorder that represents both a diagnostic and a management challenge to clinicians. Early recognition of the condition coupled with rapid institution of plasma exchange has led to a dramatic improvement in prognosis. Studies performed over the past decade have elucidated the predominant pathophysiology, stemming from a deficiency of ADAMTS13, that accounts for the widespread microvascular deposition of platelet-von Willebrand factor in many sites, including the brain, kidney, and mesenteric vessels. However, in light of the mortality rate of 10-20%, much work remains to be done to translate advances in our understanding of pathophysiology into clinical practice. Improvements in medical management using immunosuppressive and other drugs are being actively explored in clinical trials. Agents that target ADAMTS13 autoantibody production by B-cells, such as anti-CD20 monoclonal antibodies, have the potential to shorten the duration of plasma exchange treatment, reduce relapses, and transform the management of this once enigmatic disorder.

Thrombotic Thrombocytopenic Purpura Refractory to Plasmapheresis Treated Successfully with Vincristine: A Case Report

“…If not treated promptly, TTP typically follows a progressive deteriorating course with irreversible renal failure, progressive neurologic deterioration, cardiac ischemia, and death [10,11]. The immediate administration of plasma exchange has been the essential and urgent treatment for patients with a clinical diagnosis of TTP since the publication of the randomized clinical trial by the Canadian Apheresis Group in 1991 [12].…”

Von Willebrand Factor-Mediated Thrombotic Microangiopathies

“…Clinically TTP presented with a pentad of signs and symptoms: thrombocytopenia, haemolytic anemia, fever, neurologic abnormalities, and renal failure [46,47]. An increased numbers of megakaryocytes in bone marrow, alterations of erythrocytes (schistocytes), and elevated serum levels of lactate dehydrogenase (LDH) are other important features [48,49].…”

“…Hyperbilirubinemia (mainly unconjugated), reticulocytosis, circulating free hemoglobin, and low or undetectable haptoglobin levels are additional aspecific indicators of the accelerated red cell disruption and production. Indeed, a negative Coombs test is needed to confirm the microangiopathic nature of the hemolysis [46,47].…”

“…In most cases, TTP remains idiopathic, nevertheless several factors may play a role. These factors may include some diseases and conditions, such as pregnancy, postpartum period, cancer, HIV, infections, and autoimmune diseases; some medical procedures, such as surgery, total-body irradiation, and blood and marrow stem cell transplant and some drugs, such as chemotherapy, ticlopidine, clopidogrel, cyclosporine A, quinine and hormone therapy and estrogens [46][47][48][49][50].…”

Cryosupernatant and Immunosuppression as Effective Alternative Therapies for TTP in Three Pediatric SLE Patients

“…Very rarely TTP presents simultaneously with SLE [1].Moreover waiting for complete evolution of pentad features significantly delays treatment and worsens the outcome [2]. The treatment options include plasma exchange using fresh frozen plasma (FFP)/cryosupernatant (CSP) and immunosuppressive therapy [3]. Cryosupernatant is the remnant after removing cryoprecipitate [which is rich in von Willebrand factor (vWF) multimers].…”